COVID-19 - Dr. Jim Halverson

Ask Dr. Halverson: Encouraging preliminary results on oral medication for COVID-19

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By Dr. Jim Halverson
It is a hopeful time in our efforts to lessen the impact of COVID-19.
Vaccines are working. The numbers of cases and hospital admissions in our county are down substantially. We are seeing a reopening of our businesses and schools, improvements in our social opportunities, and increasing optimism that we are finally bringing this pandemic to an end, at least in many areas of our country.
Now comes more encouraging news. A five-day course of an oral antiviral medication appears to significantly decrease the viral load of SARS COV-2, the virus that causes COVID-19, in outpatients treated when first diagnosed with COVID-19.
Finding an effective oral medication for COVID-19, or any viral infection, is very difficult. For example, the common cold is also caused by a coronavirus. As scientists ruefully joke, there’s still no cure for that, despite decades of efforts and billions of dollars spent on research and development. 
The fundamental problem for scientists is that viruses don’t fight fair. When SARS-COV-2 takes hold, it  gets into our cells and begins to use our cell’s machinery to replicate itself. That gives the virus an edge. The symptoms of COVID-19 are really caused by the human host’s abnormal immune responses to it. For SARS-COV-2, it can take anywhere from a few days to two weeks for those abnormal responses to kick in. That means any clinical trial for an antiviral requires a delicate design. Patients must have confirmed infections, but if they’re already experiencing serious symptoms of COVID-19, they might be too far along to benefit. In addition, a successful drug must be able to stop viral replication early without hurting our own cells.
Despite these challenges, progress is being made. While the search for effective vaccines for COVID-19 got most of the attention, the National Institutes of Health  has been overseeing a sweeping parallel effort to find treatments for the disease itself. There have been successes. Among the bright spots has been remdesivir, an intravenous antiviral, that modestly reduces the length of hospitalizations for patients with COVID-19. The steroid dexamethasone has proved to be lifesaving for many patients who have been critically ill.  Likewise, monoclonal antibody treatments given intravenously have helped to keep high-risk patients out of the hospital.
Still missing, however, is what NIH Director Francis Collins called his “dream”: a highly effective pill that can be given immediately after diagnosis. “It is an extremely high priority of the NIH to work with companies to make sure we speed this process up,” Collins said. “Because even with great vaccines, people are still going to get sick.”
Leading contenders
The first drug to check all of the boxes of an ideal antiviral is molnupiravir, developed by Merck and Ridgeback Biotherapeutics. Drug trials proceed from Phase 1 through Phase 3. Phase 1 recruits healthy volunteers and determines if the drug is safe. That has already occurred with molnupiravir. Results of a recent Phase 2 trial, where a small number of patients with early COVID-19 were given either the medication at three different doses or a placebo, in a randomized, double-blind control trial (the gold standard for medication trials) were very encouraging. 
All groups were given one pill twice daily for five days of either the medication or placebo. By Day 5, none of the participants receiving the active drug had evidence of active SARS-COV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had active virus.
The drug’s manufacturers have now enrolled about 3,000 patients, both hospitalized and recently diagnosed, in a pivotal Phase 3 trial that will determine whether molnupiravir can help clear SARS-COV-2 from the body faster than placebo and keep patients out of the hospital. Data are expected in the coming weeks and experts are particularly focused on whether the drug can prevent patients with mild symptoms from developing severe COVID-19.
Behind Merck’s drug is a treatment from Atea Pharmaceuticals that builds on prior antiviral success. Atea’s drug, AT-527, targets an enzyme key to viral replication, a similar approach to curative treatments developed in the past several years for hepatitis C. Later this year, Atea expects to have Phase 2 data on AT-527’s benefits for patients in and out of the hospital. The company is also planning a larger, Phase 3 study on outpatients.
An oral antiviral from Pfizer, now in the earliest stages of human testing, targets SARS-COV-2’s backbone enzyme, the linchpin of the virus’s replication process. That enzyme, called 3CL, is one of two that are specific to all coronaviruses. That means if Pfizer can find the right dose and safely complete all of the trials with statistically significant results, it might have a treatment not just for SARS-COV-2, but for other coronavirus infections.
I will continue to give you updates on these trials as their results are announced. Hopefully, we will have a pill, specifically designed to treat SARS-COV-2, with tolerable side effects and a low price tag, in the not-too-distant future. 
Vaccination update
Vaccine administration in the Ojai Valley and throughout Ventura County is continuing to proceed at a very encouraging rate. In Ventura County, as of April 14, 50.2% of the population 16 and over has received at least one dose of a vaccine and 32.2% are fully vaccinated. A total of 539,570 doses have already been given countywide. I expect all of those numbers to increase substantially in the coming weeks as all people 16 and over are eligible to receive the vaccine beginning April 15.
In the Ojai Valley, the numbers are even better. In Oak View (93022), 50% of residents have received at least one dose and 30.1% are fully vaccinated. In Ojai (93023), 51% have received at least one dose and 31.9% are fully vaccinated.
One number, in particular, in the United States is also very gratifying. More than 75% of all Americans 65 and over have now received at least one dose of a vaccine. This is our most vulnerable population. In my office, nearly all patients in this age group, who I have been able to ask, have gotten the vaccine. I am so grateful for their willingness to do so, for themselves, and for all of us.
Stay hopeful, stay properly informed, follow the guidelines, stay safe and stay well.

— Dr. Jim Halverson is a longtime Ojai physician who writes a weekly column on COVID-19 for the Ojai Valley News.